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A Lundin

Publications and source records attributed to A Lundin.

At least 37 records · Page 2Linked to original sources

Brain androgen-inducible aromatase is critical for adolescent organization of environment-specific social interaction in male rats.

Previous observations have indicated that specific behavioral responses to anxiogenic stimuli emerge over adolescent development in male rats and that gonadal androgens during puberty are essential for this emergence. The objective of the current study was to evaluate mechanisms via which androgens might be organizing the brain during adolescence for appropriate mature adaptive responses. Male rats were exposed to fadrozole (an aromatase inhibitor, 5 mg/kg), flutamide (an androgen receptor antagonist, 10 mg/kg), or MK-434 (a 5 alpha-reductase inhibitor, 10 mg/kg) from day 29 to 60 and tested for environment-specific social interaction (SI) at 60 days of age. The emergence of adult-typical SI was impaired by exposure to the aromatase inhibitor and to the antiandrogen, whereas exposure to the 5 alpha-reductase inhibitor was without effect. Peripheral indices of drug effects indicated that the respective mechanisms had been altered by the different compounds. These results suggest that testosterone induction of aromatase is critical for the organization of mature SI behavior in male rats over adolescent development.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Percutaneous transluminal angioplasty with or without stenting for femoropopliteal occlusions? A randomized controlled study.

BACKGROUND: To investigate the-one year outcome of PTA and stenting and PTA alone for femoropopliteal occlusions. DESIGN: Randomized prospective study METHODS: 32 patients with femoropopliteal occlusions were randomized into two treatment groups: PTA and Strecker-stent (n=15) and PTA alone (n=17). The median age of the patients was 71 years. All patients had chronic limb ischaemia, 66% had tissue loss, 19% had rest pain and 15% had disabling claudication. The median ABPI was 0.45. The occlusion was confined to the superficial femoral artery in 30 cases and to the popliteal artery in 2 cases. The median length of the occlusions was 7.3 cm. Aspirin (ASA), 160 mg daily, was administrated postoperatively but no anticoagulation was used. The follow-up included: clinical examination, measurement of ABPI and control angiography at 12 months or earlier when necessary (20 patients). RESULTS: There was no mortality or limb loss as a consequence of the treatment. There were six (16%) immediate major complications in five patients. In the PTA group, one patient had a myocardial infarction and three patients needed arteriography due to bleeding. In the stent group, one patient required arteriography and embolectomy. The one-year mortality was 6% and there were no amputations. Four patients (two in each group) were operated on with a femorodistal bypass. The rate of clinical improvement was 71% after PTA and stent and 60% after PTA alone (p=0.17). An increased ABPI (>0.10) was shown in 50% of the stent group and 61% in the PTA group (p=0.17). Angiographic re-occlusions were seen in 33% and 75% in the stent and PTA groups respectively (p=0.17), while the rate of restenosis was significantly higher in the stent group (50% vs 25%) (p=0.033). CONCLUSIONS: Stenting following PTA for femoropopliteal occlusions does not significantly improve neither the clinical state nor the clinical/angiographic patency. The results do not justify any routine placement of stent following PTA in the successfully recanalized femoropopliteal arteries. The low rate of acceptance of a follow-up angiography indicates that this kind of study should preferably use duplex scanning instead of angiography for follow-up.

Aged↗

Improved classifications of myocardial bull's-eye scintigrams with computer-based decision support system.

UNLABELLED: In a recent study, artificial neural networks were trained to detect coronary artery disease using scintigraphic data as input. The performance of the networks was better than that of human experts using coronary angiography as a gold standard. In clinical practice, this type of neural networks will not take over the decision-making process from the physician but will assist by proposing an interpretation of the scintigram. The purpose of this study was to assess the influence of such decision support on the interpretations of the physicians. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest/stress scintigraphy and coronary angiography within a 3-mo period was studied. An image set consisting of the bull's-eye rest, stress, difference and quote images was constructed for each patient. Three experienced physicians independently classified all image sets regarding the presence and/or absence of coronary artery disease in two vascular territories using a four-grade scale. The physicians classified the image sets twice with and twice without the advice of artificial neural networks. RESULTS: The joint evaluation of the three physicians showed significantly improved performance with decision support, measured as increases in the areas under the receiver operating characteristic curves from 0.65 to 0.70 (P = 0.018) and from 0.79 to 0.82 (P = 0.006) for two vascular territories. Furthermore, the joint evaluation showed significantly less intraobserver and interobserver variability with decision support. CONCLUSION: Physicians classifying myocardial bull's-eye images benefit from the advice of artificial neural networks. These results show the high potential for neural networks as clinical decision support systems.

Adult↗

Scintigraphic diagnosis of coronary artery disease: myocardial bull's-eye images contain the important information.

The bull's-eye image, also called polar map image, has been developed as an important display for the visual and quantitative analysis of myocardial perfusion scintigrams. Quantitative analysis can be performed for example by comparing areas in the bull's-eye image with normal limits or by processing it using artificial neural networks. The usefulness of such methods is highly dependent on the information content of the bull's-eye image. The purpose of this study was to investigate whether there is more diagnostically important information in a set consisting of the myocardial bull's-eye image plus tomographic slice image than in the bull's-eye image alone. A population of 135 patients who had undergone both myocardial scintigraphy and coronary angiography, with no more than 3 months elapsing between the two examinations, was studied retrospectively. Four experienced observers independently classified visually all scintigrams regarding the presence/absence of coronary artery disease in two vascular territories using a four-grade scale. The observers classified the scintigrams once viewing bull's-eye images only, and once viewing tomographic slices and bull's-eye images. Coronary angiography was used as gold standard. The classifications were evaluated using the areas under the receiver operating characteristics (ROC) curves. The classifications based on bull's-eye images only were slightly more accurate than those based on tomographic slices and bull's-eye images in one of the two vascular territories (ROC areas of 0.66 vs. 0.64). The opposite relationship was found in the other vascular territory (0.78 vs. 0.81). None of the differences was statistically significant. In conclusion, the diagnostically important information for the diagnosis of coronary artery disease by myocardial perfusion scintigraphy is present in the bull's-eye image.

Adult↗

A luminometric assay for determination of ethanol in microdialysates.

In microdialysis, samples from the extracellular fluid are analysed in the outgoing dialysate. By adding ethanol to the ingoing perfusate and following its exchange in the dialysate, an outflow/inflow ratio is obtained. This ratio has been shown to correlate with the tissue blood flow. An automatic luminometric ethanol assay that quantifies the light produced from three coupled enzyme reactions is described. Alcohol dehydrogenase catalyses the oxidation of ethanol with formation of NADH, which is monitored using NADH:FMN oxidoreductase and bacterial luciferase. Each assay can be individually calibrated by measuring the increased rate of NADH formation through the addition of a known amount of ethanol. The linear range of the assay was 0.05-10 mmol l-1 in microdialysate samples. The within-run imprecision was 1.4% CV in 10 mmol l-1 samples, and ethanol recovery was almost 100%. The assay was applied to microdialysates that were generated from probes implanted in the vastus lateralis muscle in fasting subjects (n = 12) and perfused with 5 mmol l-1 ethanol at 3 microliter min-1. An outflow/inflow steady-state ratio of 27% (range 19-47%) appeared after about 1 h, followed by a within-run variability of 4.7% CV (range 2.5-7.7% CV), as calculated from samples collected every 15 min up to 4 h after stabilization. In conclusion, a sensitive ethanol assay, suitable for studies of microcirculatory exchange of solute molecules over the dialysis probe is presented.

Alcohol Dehydrogenase↗

A Huntington disease-like neurodegenerative disorder maps to chromosome 20p.

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor disturbance, cognitive loss, and psychiatric manifestations. The disease is associated with a CAG trinucleotide-repeat expansion in the Huntington gene (IT15) on chromosome 4p16.3. One family with a history of HD was referred to us initially for predictive testing using linkage analysis. However, the chromosome 4p region was completely excluded by polymorphic markers, and later no CAG-repeat expansion in the HD gene was detected. To map the disease trait segregating in this family, whole-genome screening with highly polymorphic dinucleotide-, trinucleotide-, and tetranucleotide-repeat DNA markers was performed. A positive LOD score of 3.01 was obtained for the marker D20S482 on chromosome 20p, by two-point LOD-score analysis with the MLINK program. Haplotype analysis indicated that the gene responsible for the disease is likely located in a 2.7-cM region between the markers D20S193 and D20S895. Candidate genes from the mapping region were screened for mutations.

Adult↗

Larger CAG expansions in skeletal muscle compared with lymphocytes in Kennedy disease but not in Huntington disease.

The size of CAG repeats was compared in lymphocytes and skeletal muscle from nine patients with Huntington disease (HD) and two patients with Kennedy disease (KD). In HD, the number of CAG repeats did not differ between lymphocytes and skeletal muscle. In the two KD patients, however, the CAG expansion was larger in muscle than in lymphocytes. The difference in trinucleotide expansion between lymphocytes and muscle cells is not a universal phenomenon in trinucleotide repeat disorders, but seems to occur in disorders primarily affecting the neuromuscular system.

Aged↗

Luminometric single step urea assay using ATP-hydrolyzing urease.

An automatic enzyme kinetic luminometric method for determination of small quantities of urea in biological fluids and in microdialysates is presented. The method is based on the ATP-hydrolyzing urease reaction [urea amidohydrolase (ATP-hydrolyzing); EC 3.5.1.45], monitored by a luciferin-luciferase ATP reaction. The assay range is 100 pmol to 50 nmol with a detection limit of 5 micromol/L in the sample, compared with detection limits of 0.1 mmol/L in earlier spectrophotometric methods. To reduce the non-urea-dependent ATPase activity (v(blank)) and to increase the urea-dependent activity, 1,2-propanediol was included. Assay conditions were optimized by multivariate analysis. Recoveries of urea added to blood dialysate and plasma were 96-103%. No analytical interference of common metabolites, drugs, or other additives was observed. The total CVs (6 days and six concentrations, 1.2-21.8 mmol/L) were 3.6-8.5%. The results obtained with the present assay were highly correlated for dialysate (r = 0.979) and for plasma (r = 0.978) with those obtained by a spectrophotometric kit method with slopes of 1.02-1.03 and intercepts of 0.08-0.23 mmol/L.

Adenosine Triphosphate↗

Reactions to predictive testing in Huntington disease: case reports of coping with a new genetic status.

A predictive testing program for Huntington disease has been available in Stockholm, Sweden since October 1990. Psychosocial assessments were performed throughout the testing program to evaluate the impact of the risk situation itself and the effect of predictive testing, and to identify those individuals who were most vulnerable to severe stress and anxiety reactions. All subjects underwent neurological, neuropsychological, and psychiatric examinations. Individuals undergoing predictive testing were assessed twice by a genetic counsellor before receiving their results, and at 10 days (gene carriers only) and then 2, 6, 12, and 24 months after receiving the results. The process of coping with the test results and the psychological adjustment to knowledge about new genetic status have been shown to vary considerably. In this report, we describe the results obtained from two gene carriers and two noncarriers. The four persons chosen represent different ways of coping with the outcome of the test and of integrating knowledge about their genetic status into everyday life. These cases illustrate common themes and recurrent problems often surfacing during the counselling and testing process. The longitudinal evaluations provide information about the impact, adaptation, and long-term effects of living with a new genetic status.

Adaptation, Psychological↗

Cognitive deficits in Huntington's disease are predicted by dopaminergic PET markers and brain volumes.

The main aim of this study was to investigate the relationship between dopaminergic markers and brain volumes for striatal and cortical structures, and cognitive performance in patients with Huntington's disease and control subjects. We used PET and MRI data as predictors of performance in tasks assessing executive function, visuospatial ability, episodic memory, verbal fluency, perceptual speed and reasoning. The dopamine neurotransmission parameters (D1 and D2 receptor density and dopamine transporter density) and the volumetric measurements for caudate and putamen accounted for substantial portions of the variance across the majority of cognitive tasks. In addition, frontal volume showed a strong relationship with all cognitive tasks. D1 binding and volume measurements for the temporal cortex and thalamic volume showed associations with a select number of cognitive tasks. The overall data pattern is consistent with the view that Huntington's disease may be characterized as a frontostriatal dementia, in which cognitive deficits may result from pathological changes at multiple sites in the frontostriatal circuitry.

Benzazepines↗

PET study of the pre- and post-synaptic dopaminergic markers for the neurodegenerative process in Huntington's disease.

PET and: markers for the pre- and postsynaptic neurons were used to study the dopamine system in vivo in Huntington's disease. The radioligands used were [11C]SCH 23390 for D1-receptors, [11C]raclopride for D2-receptors and [11C]beta-CIT for dopamine transporters. Five patients with Huntington's disease and five matched controls were recruited. Brain anatomy was examined by MRI. The findings in patients were as follows. Postsynaptic D1- and D2-receptor densities were similarly reduced in the striatum. A reduction in D1-receptor density was shown in the temporal cortex; it draws attention to the cortical degeneration in relation to the cognitive deficits observed in Huntington's disease. The reduction of D1- and D2-receptor binding potentials in the striatum correlated significantly with increasing duration of illness. The correlation between the duration of illness and decline of D1- and D2-receptors make these receptors valuable as quantitative markers for the Huntington's disease degenerative process. Besides postsynaptic changes, a significant 50% decrease of [11C]beta-CIT binding to the dopamine transporter was found in the striatum. A reduced striatal blood flow in Huntington's disease cannot be excluded and could account for a small part of the decrease in [11C]beta-CIT binding. We suggest that the finding reflects a loss of presynaptic terminals or a reduced expression of dopamine transporter in the nigrostriatal dopaminergic system in Huntington's disease.

Adult↗

Radical endarterectomy of severely calcified ascending aorta prevents stroke during open-heart surgery.

In ten patients (7 women), mean age 73 years, with severely calcified ascending aorta, aortic valve and coronary artery disease were surgically treated after radical endarterectomy of the ascending aorta during cardiopulmonary bypass and with or without deep hypothermic total circulatory arrest. One patient died 10 days and one 11 months postoperatively of complications which neither directly nor indirectly could be attributed to the aortic endarterectomy. The eight surviving patients are doing well after follow-up averaging 16 months. CT scans 1 year postoperatively showed no aneurysmal dilation of the ascending aorta or aortic dissection distal to the endarterectomy site. Radical endarterectomy of calcified ascending aorta thus can be performed with relatively low mortality and stroke risk and may be considered in patients undergoing valve replacement and/or coronary artery bypass grafting.

Aged↗

Automated interpretation of myocardial SPECT perfusion images using artificial neural networks.

UNLABELLED: The purpose of this study was to develop a computer-based method for automatic detection and localization of coronary artery disease (CAD) in myocardial bull's-eye scintigrams. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest-stress scintigraphy and coronary angiography within 3 mo was studied. Different image data reduction methods, including pixel averaging and two-dimensional Fourier transform, were applied to the bull's-eye scintigrams. After a quantitative and qualitative evaluation of these methods, 30 Fourier components were chosen as inputs to multilayer perceptron artificial neural networks. The networks were trained to detect CAD in two vascular territories, using coronary angiography as gold standard. A "leave one out" procedure was used for training and evaluation. The performance of the networks was compared to those of two human experts. RESULTS: One of the human experts detected CAD in one of two vascular territories, with a sensitivity of 54.4% at a specificity of 70.5%. The sensitivity of the networks was significantly higher at that level of specificity (77.2%, p = 0.0022). The other expert had a sensitivity of 63.2% at a specificity of 61.5%. The networks had a sensitivity of 77.2% (p = 0.038) at this specificity level as well. The differences in sensitivity between human experts and networks for the other vascular territory were all less than 6% and were not statistically significant. CONCLUSION: Artificial neural networks can detect CAD in myocardial bull's-eye scintigrams with such a high accuracy that the application of neural networks as clinical decision support tools appears to have significant potential.

Coronary Angiography↗

Improved pulmonary function in systemic sclerosis after treatment with cyclophosphamide.

OBJECTIVE: Pulmonary fibrosis is a common feature of systemic sclerosis (SSc) and a major cause of morbidity and mortality. Since alveolitis may be an essential step in the development of pulmonary fibrosis, we investigated the use of immunosuppressive drug therapy to improve pulmonary function in patients with SSc. METHODS: Eighteen patients with progressive pulmonary dysfunction, diminished vital capacity (VC), and/or decreased static lung compliance (Cst) were treated with cyclophosphamide and corticosteroids for 1 year. Eight patients had diffuse cutaneous SSc and 10 had limited cutaneous SSc. The median disease duration was 2.5 years (range 0.5-17 years). RESULTS: VC increased in 14 of 18 patients and the median VC rose from 74% to 80% of predicted. Cst improved in 8 of 12 patients and the median Cst increased from 59% to 66% of predicted. Pulmonary nonfibrotic opacities disappeared in 9 of 12 patients. The erythrocyte sedimentation rate (ESR) and serum concentrations of orosomucoid, C-reactive protein, and aminopropeptide type III collagen all improved. The patients were divided into 2 groups based on the presence or absence of elevations in acute-phase protein levels and ESR before therapy. Among the 12 patients with biochemical signs of inflammation, VC increased in 11, and Cst improved or was unchanged in 7 of the 8 who were tested. The median VC in this subgroup increased from 73% to 80% of predicted and the median Cst increased from 57% to 60% of predicted. In the group of 18 patients overall, the skin score decreased, while esophageal and renal function remained stable. CONCLUSION: Cyclophosphamide may have a beneficial effect on pulmonary fibrosis in patients with SSc and elevated levels of acute-phase proteins. Controlled trials of cyclophosphamide in pulmonary SSc should be performed and should focus on such patients.

Adult↗